Neural tube defects (NTD) are an important cause of neonatal death, or subsequent mental retardation, chronic invalidism and decreased life expectancy. Approximately 8,000 babies with these defects are born each year in the U.S.A. The disastrous emotional, family and economic consequences of these defects provide cogent reasons for priority attention to be given to their prevention. Preliminary data suggests that the most significant advances in prevention may well be the use of fetal or brain specific proteins in early detection through prenatal diagnosis. In our initial fluid alpha-fetoprotein (AFP) studies, we have examined over 800 cases. In delineating the normal range of amniotic fluid AFP levels in the second trimester of pregnancy, we have also studied 13 fetuses with neural tube defects, in addition to 43 cases with other fetal defects or associated obstetric complications. The primary objectives are to do comparative and complementary studies to determine: 1. the usefulness and specificity of alpha-fetoprotein and CSF beta-trace protein estimations in the prenatal detection of neural tube defects; 2. the most reliable, accurate and applicable methodology for diagnostic assays for each of these proteins; 3. in addition, the pathophysiology of AFP synthesis and secretion in fetuses with anencephaly and myelomeningocele will be studied. These objectives will be achieved through extensive study using comparative assays on plus or minus 3,300 amniotic fluid samples, and through studies on fetal tissues obtained at abortion. In addition prospective prenatal study of maternal serum (plus or minus 8,000 cases) followed when indicated by amniotic fluid studies of both AFP and beta-trace protein will be studied. The specificity, validity, accuracy and possible complementary use of these protein estimations in the prenatal detection of NTD using amniotic fluid and maternal serum should be clearly established by these studies. BIBLIOGRAPHIC REFERENCES: Milunsky, A.: Alpha-fetoprotein and the prenatal diagnosis of neural tube defects. Contemporary OB/GYN 6:59, 1975. Milunsky, A., Macri, J.N., Weiss, R.R., Alpert, E., McIsaac, D.G. and Joshi, M.S.: Prenatal detection of neural tube defects. Comparison between alpha-fetoprotein and beta-trace protein assays. Amer. J. Obstet. Gynecol. 122:313, 1975.